cci-779 in treating patients with malignant glioma

Conditions: Brain and Central Nervous System Tumors

Summary: rationale: drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. purpose: phase i/ii trial to study the effectiveness of cci-779 in treating patients who have malignant glioma.

objectives: * determine the maximum tolerated dose of cci-779 in patients with malignant glioma. * determine the safety profile of this drug in these patients. * determine the pharmacokinetics of this drug in these patients. * determine the efficacy of this drug, in terms of survival and objective response, in these patients. outline: this is a dose-escalation study. patients in phase ii are stratified according to use of enzyme-inducing antiepileptic drugs (eiaeds) (yes vs no) and disease type (glioblastoma multiforme with stable neuro-imaging after radiotherapy vs recurrent malignant glioma). patients in phase i must be currently receiving eiaeds. * phase i: patients receive cci-779 iv over 30 minutes once weekly. treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. cohorts of 3-6 patients receive escalating doses of cci-779 until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. * phase ii: patients receive cci-779 as in phase i. patients who are candidates for surgical resection of recurrent disease receive cci-779 iv over 30 minutes 2 hours prior to surgery and then once weekly, as above, once recovered from surgery. patients are followed for survival. projected accrual: a total of 36 patients will be accrued for phase i of this study within 12 months. a total of 87 patients will be accrued for phase ii of this study within 12 months.

Eligibility criteria:
disease characteristics: * histologically confirmed intracranial malignant glioma * glioblastoma multiforme * anaplastic astrocytoma * anaplastic oligodendroglioma * anaplastic mixed oligoastrocytoma * malignant astrocytoma not otherwise specified * initial diagnosis of low-grade allowed, if subsequently progressed * recurrent disease must have documented progression by mri or ct scan * progressive disease must have failed prior radiotherapy * recent resection of recurrent or progressive tumor allowed provided all of the following are met: * recovered from surgery * ct scan or mri performed no more than 96 hours postoperatively or at 4-6 weeks postoperatively * concurrent steroid dosage must be stable * confirmation of true progressive disease (by pet, thallium scan, mr spectroscopy, or surgical documentation) required after prior interstitial brachytherapy or stereotactic radiosurgery patient characteristics: age: * 18 and over performance status: * karnofsky 60-100% life expectancy: * more than 8 weeks hematopoietic: * wbc at least 3,000/mm3 * absolute neutrophil count at least 2,000/mm3 * platelet count at least 120,000/mm3 * hemoglobin at least 10 g/dl (transfusion allowed) hepatic: * bilirubin less than 1.5 times upper limit of normal (uln) * sgot less than 1.5 times uln * cholesterol less than 350 mg/dl * triglycerides less than 400 mg/dl renal: * creatinine less than 1.5 mg/dl * creatinine clearance at least 60 ml/min other: * no active infection * no other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix * no significant medical illness that would preclude study * no disease that would obscure toxicity or dangerously alter drug metabolism * no history of allergic reactions attributed to compounds of similar chemical or biologic composition to cci-779 or allergy to or inability to receive antihistamines * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception during and for 12 weeks after study prior concurrent therapy: biologic therapy: * at least 1 week since prior interferon chemotherapy: * at least 2 weeks since prior vincristine * at least 3 weeks since prior procarbazine * at least 6 weeks since prior nitrosoureas * phase i: * 2 prior chemotherapy regimens allowed * 1 prior adjuvant regimen and 1 prior regimen for recurrent or progressive disease or * 2 prior regimens for progressive tumor * phase ii: * no more than 1 prior chemotherapy regimen for recurrent malignant glioma * no prior chemotherapy allowed for stable glioblastoma multiforme endocrine therapy: * see disease characteristics * at least 1 week since prior tamoxifen radiotherapy: * see disease characteristics * at least 4 weeks since prior radiotherapy for progressive disease * no more than 1 month since prior radiotherapy for nonprogressive glioblastoma multiforme surgery: * see disease characteristics other: * recovered from prior therapy * at least 1 week since prior noncytotoxic agents

Keywords: recurrent adult brain tumor adult glioblastoma adult anaplastic astrocytoma adult anaplastic oligodendroglioma adult mixed glioma adult giant cell glioblastoma adult gliosarcoma